Adenovirus infections in immunocompromised human beings are more prevalent, persistent, and severe than in the normal host. A spectrum of localized or generalized infections are associated with specific adenovirus serotypes. Similarly, in immunosuppressed rhesus monkeys, non-human primate adenovirus serotypes SV31, 20, 23, and 15 have been associated with pancreatic disease and serotype SV11 with enterocolitis. However, the organ-specific tropism of these specific isolates has not been investigated in immunosuppressed macaques. There have been fifteen cases of adenovirus-associated disease in SIVmac-infected macaques at the NERPRC. All six cases prior to 1987 were associated with necrotizing pancreatitis and adenovirus serotype SV11 was isolated from one of these cases. In the following seven years eight additional cases of adenovirus have been observed in SIVmac-infected macaques, but, disease was limited to the intestinal tract in all eight cases. Three of these cases were culture-positive for adenovirus serotype SV11. These results suggest that organ-tropism of adenovirus serotypes may change over time. Attempts to reproduce that disease in immunosuppressed macaques utilizing these putative enterotropic and pancreotropic isolates of adenovirus serotype SV11 have been unsuccessful. Thus, despite profound immunosuppresion pre-exposure to adenovirus in these macaques was apparently protective. Further studies are needed to examine the protective role of adenovirus-specific antibody titers during the course of infection.